Medical Genetics Commons^™

Deep Learning Integrates Histopathology And Proteogenomics At A Pan-Cancer Level, Joshua M Wang, Runyu Hong, Elizabeth G Demicco, Jimin Tan, Rossana Lazcano, Andre L Moreira, Yize Li, Anna Calinawan, Narges Razavian, Tobias Schraink, Michael A Gillette, Gilbert S Omenn, Eunkyung An, Henry Rodriguez, Aristotelis Tsirigos, Kelly V Ruggles, Li Ding, Ana I Robles, D R Mani, Karin D Rodland, Alexander J Lazar, Wenke Liu, David Fenyö, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Student Publications

We introduce a pioneering approach that integrates pathology imaging with transcriptomics and proteomics to identify predictive histology features associated with critical clinical outcomes in cancer. We utilize 2,755 H&E-stained histopathological slides from 657 patients across 6 cancer types from CPTAC. Our models effectively recapitulate distinctions readily made by human pathologists: tumor vs. normal (AUROC = 0.995) and tissue-of-origin (AUROC = 0.979). We further investigate predictive power on tasks not normally performed from H&E alone, including TP53 prediction and pathologic stage. Importantly, we describe predictive morphologies not previously utilized in a clinical setting. The incorporation of transcriptomics and proteomics identifies pathway-level …

Sepepquant Enhances The Detection Of Possible Isoform Regulations In Shotgun Proteomics, Yongchao Dou, Yuejia Liu, Xinpei Yi, Lindsey K Olsen, Hongwen Zhu, Qiang Gao, Hu Zhou, Bing Zhang

Faculty, Staff and Students Publications

Shotgun proteomics is essential for protein identification and quantification in biomedical research, but protein isoform characterization is challenging due to the extensive number of peptides shared across proteins, hindering our understanding of protein isoform regulation and their roles in normal and disease biology. We systematically assess the challenge and opportunities of shotgun proteomics-based protein isoform characterization using in silico and experimental data, and then present SEPepQuant, a graph theory-based approach to maximize isoform characterization. Using published data from one induced pluripotent stem cell study and two human hepatocellular carcinoma studies, we demonstrate the ability of SEPepQuant in addressing the key …

A Multicenter Analysis Of Abnormal Chromosomal Microarray Findings In Congenital Heart Disease, Benjamin J Landis, Lindsey R Helvaty, Gabrielle C Geddes, Jiuann-Huey Ivy Lin, Svetlana A Yatsenko, Cecilia W Lo, William L Border, Stephanie Burns Wechsler, Chaya N Murali, Mahshid S Azamian, Seema R Lalani, Robert B Hinton, Vidu Garg, Kim L Mcbride, Jennelle C Hodge, Stephanie M Ware

Faculty, Staff and Students Publications

Background

Chromosomal microarray analysis (CMA) provides an opportunity to understand genetic causes of congenital heart disease (CHD). The methods for describing cardiac phenotypes in patients with CMA abnormalities have been inconsistent, which may complicate clinical interpretation of abnormal testing results and hinder a more complete understanding of genotype–phenotype relationships.

Methods and Results

Patients with CHD and abnormal clinical CMA were accrued from 9 pediatric cardiac centers. Highly detailed cardiac phenotypes were systematically classified and analyzed for their association with CMA abnormality. Hierarchical classification of each patient into 1 CHD category facilitated broad analyses. Inclusive classification allowing multiple CHD types per …

Neurocognitive Outcomes In Adult Survivors Of Neuroblastoma: A Report From The Childhood Cancer Survivor Study, Caroline Hesko, Wei Liu, Deo K Srivastava, Tara M Brinkman, Lisa Diller, Todd M Gibson, Kevin C Oeffinger, Wendy M Leisenring, Rebecca Howell, Gregory T Armstrong, Kevin R Krull, Tara O Henderson

Faculty, Staff and Student Publications

Background: Despite survival improvements, there is a paucity of data on neurocognitive outcomes in neuroblastoma survivors. This study addresses this literature gap.

Methods: Neurocognitive impairments in survivors were compared to sibling controls from the Childhood Cancer Survivor Study (CCSS) using the CCSS Neurocognitive Questionnaire. Impaired emotional regulation, organization, task efficiency, and memory defined as scores ≥90th percentile of sibling norms. Modified Poisson regression models evaluated associations with treatment exposures, era of diagnosis, and chronic conditions. Analyses were stratified by age at diagnosis (≤1 and >1 year) as proxy for lower versus higher risk disease.

Results: Survivors (N = 837; median …

Single Cell Multiomics Identifies Cells And Genetic Networks Underlying Alveolar Capillary Dysplasia, Minzhe Guo, Kathryn A Wikenheiser-Brokamp, Joseph A Kitzmiller, Cheng Jiang, Guolun Wang, Allen Wang, Sebastian Preissl, Xiaomeng Hou, Justin Buchanan, Justyna A Karolak, Yifei Miao, David B Frank, William J Zacharias, Xin Sun, Yan Xu, Mingxia Gu, Pawel Stankiewicz, Vladimir V Kalinichenko, Jennifer A Wambach, Jeffrey A Whitsett

Faculty, Staff and Students Publications

Rationale

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal developmental disorder of lung morphogenesis caused by insufficiency of FOXF1 (forkhead box F1) transcription factor function. The cellular and transcriptional mechanisms by which FOXF1 deficiency disrupts human lung formation are unknown.

Objectives

To identify cell types, gene networks, and cell–cell interactions underlying the pathogenesis of ACDMPV.

Methods

We used single-nucleus RNA and assay for transposase-accessible chromatin sequencing, immunofluorescence confocal microscopy, and RNA in situ hybridization to identify cell types and molecular networks influenced by FOXF1 in ACDMPV lungs.

Measurements and Main Results

Pathogenic single-nucleotide variants and copy-number …

Pathogen-Driven Crispr Screens Identify Trex1as A Regulator Of Dna Self-Sensing During Influenza Virus Infection, Cason R King, Yiping Liu, Katherine A Amato, Grace A Schaack, Clayton Mickelson, Autumn E Sanders, Tony Hu, Srishti Gupta, Ryan A Langlois, Judith A Smith, Andrew Mehle

Faculty, Staff and Student Publications

Host:pathogen interactions dictate the outcome of infection, yet the limitations of current approaches leave large regions of this interface unexplored. Here, we develop a novel fitness-based screen that queries factors important during the middle to late stages of infection. This is achieved by engineering influenza virus to direct the screen by programming dCas9 to modulate host gene expression. Our genome-wide screen for pro-viral factors identifies the cytoplasmic DNA exonuclease TREX1. TREX1 degrades cytoplasmic DNA to prevent inappropriate innate immune activation by self-DNA. We reveal that this same process aids influenza virus replication. Infection triggers release of mitochondrial DNA into the …

Precision Modulation Of Dysbiotic Adult Microbiomes With A Human-Milk-Derived Synbiotic Reshapes Gut Microbial Composition And Metabolites, Julie E Button, Casey M Cosetta, Abigail L Reens, Sarah L Brooker, Aislinn D Rowan-Nash, Richard C Lavin, Russell Saur, Shuning Zheng, Chloe A Autran, Martin L Lee, Adam K Sun, Amin M Alousi, Christine B Peterson, Andrew Y Koh, David J Rechtman, Robert R Jenq, Gregory J Mckenzie

Faculty, Staff and Student Publications

Manipulation of the gut microbiome using live biotherapeutic products shows promise for clinical applications but remains challenging to achieve. Here, we induced dysbiosis in 56 healthy volunteers using antibiotics to test a synbiotic comprising the infant gut microbe, Bifidobacterium longum subspecies infantis (B. infantis), and human milk oligosaccharides (HMOs). B. infantis engrafted in 76% of subjects in an HMO-dependent manner, reaching a relative abundance of up to 81%. Changes in microbiome composition and gut metabolites reflect altered recovery of engrafted subjects compared with controls. Engraftment associates with increases in lactate-consuming Veillonella, faster acetate recovery, and changes in indolelactate and p-cresol …

Global Impact Of Somatic Structural Variation On The Cancer Proteome, Fengju Chen, Yiqun Zhang, Darshan S Chandrashekar, Sooryanarayana Varambally, Chad J Creighton

Faculty, Staff and Students Publications

Both proteome and transcriptome data can help assess the relevance of non-coding somatic mutations in cancer. Here, we combine mass spectrometry-based proteomics data with whole genome sequencing data across 1307 human tumors spanning various tissues to determine the extent somatic structural variant (SV) breakpoint patterns impact protein expression of nearby genes. We find that about 25% of the hundreds of genes with SV-associated cis-regulatory alterations at the mRNA level are similarly associated at the protein level. SVs associated with enhancer hijacking, retrotransposon translocation, altered DNA methylation, or fusion transcripts are implicated in protein over-expression. SVs combined with altered protein levels …

Integrative Multi-Omic Cancer Profiling Reveals Dna Methylation Patterns Associated With Therapeutic Vulnerability And Cell-Of-Origin, Wen-Wei Liang, Rita Jui-Hsien Lu, Reyka G Jayasinghe, Steven M Foltz, Eduard Porta-Pardo, Yifat Geffen, Michael C Wendl, Rossana Lazcano, Iga Kolodziejczak, Yizhe Song, Akshay Govindan, Elizabeth G Demicco, Xiang Li, Yize Li, Sunantha Sethuraman, Samuel H Payne, David Fenyö, Henry Rodriguez, Maciej Wiznerowicz, Hui Shen, D R Mani, Karin D Rodland, Alexander J Lazar, Ana I Robles, Li Ding, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Student Publications

DNA methylation plays a critical role in establishing and maintaining cellular identity. However, it is frequently dysregulated during tumor development and is closely intertwined with other genetic alterations. Here, we leveraged multi-omic profiling of 687 tumors and matched non-involved adjacent tissues from the kidney, brain, pancreas, lung, head and neck, and endometrium to identify aberrant methylation associated with RNA and protein abundance changes and build a Pan-Cancer catalog. We uncovered lineage-specific epigenetic drivers including hypomethylated FGFR2 in endometrial cancer. We showed that hypermethylated STAT5A is associated with pervasive regulon downregulation and immune cell depletion, suggesting that epigenetic regulation of STAT5A …

Krasg12d Inhibition Reprograms The Tumor Microenvironment Of Early And Advanced Pancreatic Cancer To Promote Fas-Mediated Killing By Cd8+ T Cells, Krishnan K Mahadevan, Kathleen M Mcandrews, Valerie S Lebleu, Sujuan Yang, Hengyu Lyu, Bingrui Li, Amari M Sockwell, Michelle L Kirtley, Sami J Morse, Barbara A Moreno Diaz, Michael P Kim, Ningping Feng, Anastasia M Lopez, Paola A Guerrero, Francesca Paradiso, Hikaru Sugimoto, Kent A Arian, Haoqiang Ying, Yasaman Barekatain, Lakshmi Kavitha Sthanam, Patience J Kelly, Anirban Maitra, Timothy P Heffernan, Raghu Kalluri

Faculty, Staff and Student Publications

The KRASG12D mutation is present in nearly half of pancreatic adenocarcinomas (PDAC). We investigated the effects of inhibiting the KRASG12D mutant protein with MRTX1133, a non-covalent small molecule inhibitor of KRASG12D, on early and advanced PDAC and its influence on the tumor microenvironment. Employing 16 different models of KRASG12D-driven PDAC, we demonstrate that MRTX1133 reverses early PDAC growth, increases intratumoral CD8+ effector T cells, decreases myeloid infiltration, and reprograms cancer associated fibroblasts. MRTX1133 leads to regression of both established PanINs and advanced PDAC. Regression of advanced PDAC requires CD8+ T cells and immune checkpoint blockade (ICB) synergizes with MRTX1133 …

Elimination Of Oncogenic Kras In Genetic Mouse Models Eradicates Pancreatic Cancer By Inducing Fas-Dependent Apoptosis By Cd8+ T Cells, Krishnan K Mahadevan, Valerie S Lebleu, Elena V Ramirez, Yang Chen, Bingrui Li, Amari M Sockwell, Mihai Gagea, Hikaru Sugimoto, Lakshmi Kavitha Sthanam, Desiree Tampe, Michael Zeisberg, Haoqiang Ying, Abhinav K Jain, Ronald A Depinho, Anirban Maitra, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Oncogenic KrasG12D (Kras*) is critical for the initiation and maintenance of pancreatic ductal adenocarcinoma (PDAC), and a known repressor of tumor immunity. Conditional elimination of Kras* in genetic mouse models of PDAC leads to reactivation of Fas, CD8+ T cell mediated apoptosis, and complete eradication of tumors. Kras* elimination recruits activated CD4+ and CD8+ T cells and promotes the activation of antigen presenting cells. Mechanistically, Kras* mediated immune evasion involves epigenetic regulation of the Fas death receptor in cancer cells, via methylation of its promoter region. Further, analysis of human RNA sequencing identifies that high KRAS expressing PDAC tumors show …

Treatment Of Older Adults With Flt3-Mutated Aml: Emerging Paradigms And The Role Of Frontline Flt3 Inhibitors, Nicholas J Short, Daniel Nguyen, Farhad Ravandi

Faculty, Staff and Student Publications

FLT3 is the most frequently mutated gene in acute myeloid leukemia (AML), with FLT3 internal tandem duplication (ITD) mutations being associated with a more aggressive clinical course. While two large, randomized clinical trials have shown a survival benefit with the frontline use of an oral FLT3 inhibitor (midostaurin or quizartinib) in patients with FLT3-mutated AML, the role of FLT3 inhibitors in older adults with newly diagnosed FLT3-mutated AML remains unclear. A definitive improvement in survival has not been observed in intensively treated patients over 60 years of age receiving frontline FLT3 inhibitors. Furthermore, many patients with FLT3-mutated AML are unsuitable …

Phasedancer: A Novel Targeted Assembler Of Segmental Duplications Unravels The Complexity Of The Human Chromosome 2 Fusion Going From 48 To 46 Chromosomes In Hominin Evolution, Barbara Poszewiecka, Krzysztof Gogolewski, Justyna A Karolak, Paweł Stankiewicz, Anna Gambin

Faculty, Staff and Students Publications

Resolving complex genomic regions rich in segmental duplications (SDs) is challenging due to the high error rate of long-read sequencing. Here, we describe a targeted approach with a novel genome assembler PhaseDancer that extends SD-rich regions of interest iteratively. We validate its robustness and efficiency using a golden-standard set of human BAC clones and in silico-generated SDs with predefined evolutionary scenarios. PhaseDancer enables extension of the incomplete complex SD-rich subtelomeric regions of Great Ape chromosomes orthologous to the human chromosome 2 (HSA2) fusion site, informing a model of HSA2 formation and unravelling the evolution of human and Great Ape genomes.

Five-Year Follow-Up Of Keynote-087: Pembrolizumab Monotherapy For Relapsed/Refractory Classical Hodgkin Lymphoma, Philippe Armand, Pier Luigi Zinzani, Hun Ju Lee, Nathalie A Johnson, Pauline Brice, John Radford, Vincent Ribrag, Daniel Molin, Theodoros P Vassilakopoulos, Akihiro Tomita, Bastian Von Tresckow, Margaret A Shipp, Alex F Herrera, Jianxin Lin, Eunhee Kim, Samhita Chakraborty, Patricia Marinello, Craig H Moskowitz

Faculty, Staff and Student Publications

Previous analyses of the phase 2 KEYNOTE-087 (NCT02453594) trial of pembrolizumab monotherapy demonstrated effective antitumor activity with acceptable safety in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL). However, long-term response durability and outcome of patients who receive a second course after treatment discontinuation after complete response (CR) remain of clinical interest. We present KEYNOTE-087 data after >5 years of median follow-up. Patients with R/R cHL and progressive disease (PD) after autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV; cohort 1), salvage chemotherapy and BV without ASCT (cohort 2), or ASCT without subsequent BV (cohort 3), received …

Seamless Phase Ii/Iii Design: A Useful Strategy To Reduce The Sample Size For Dose Optimization, Liyun Jiang, Ying Yuan

Faculty, Staff and Student Publications

Background: The traditional more-is-better dose selection paradigm, originally developed for cytotoxic chemotherapeutics, can be problematic when applied to the development of novel molecularly targeted agents. Recognizing this issue, the US Food and Drug Administration initiated Project Optimus to reform the dose optimization and selection paradigm in oncology drug development, emphasizing the need for greater attention to benefit-risk considerations.

Methods: We identify different types of phase II/III dose-optimization designs, classified according to trial objectives and endpoint types. Through computer simulations, we examine their operating characteristics and discuss the relevant statistical and design considerations for effective dose optimization.

Results: Phase II/III dose-optimization …

Integrating Participant Feedback And Concerns To Improve Community And Individual Level Chemical Exposure Assessment Reports, Samantha M Samon, Michael Barton, Kim Anderson, Abiodun Oluyomi, Melissa Bondy, Georgina Armstrong, Diana Rohlman

Faculty, Staff and Students Publications

BACKGROUND: As exposure assessment has shifted towards community-engaged research there has been an increasing trend towards reporting results to participants. Reports aim to increase environmental health literacy, but this can be challenging due to the many unknowns regarding chemical exposure and human health effects. This includes when reports encompass a wide-range of chemicals, limited reference or health standards exist for those chemicals, and/or incompatibility of data generated from exposure assessment tools with published reference values (e.g., comparing a wristband concentration to an oral reference dose).

METHODS: Houston Hurricane Harvey Health (Houston-3H) participants wore silicone wristbands that were analyzed for 1,530 …

Aenmd: Annotating Escape From Nonsense-Mediated Decay For Transcripts With Protein-Truncating Variants, Jonathan Klonowski, Qianqian Liang, Zeynep Coban-Akdemir, Cecilia Lo, Dennis Kostka

Faculty, Staff and Student Publications

DNA changes that cause premature termination codons (PTCs) represent a large fraction of clinically relevant pathogenic genomic variation. Typically, PTCs induce transcript degradation by nonsense-mediated mRNA decay (NMD) and render such changes loss-of-function alleles. However, certain PTC-containing transcripts escape NMD and can exert dominant-negative or gain-of-function (DN/GOF) effects. Therefore, systematic identification of human PTC-causing variants and their susceptibility to NMD contributes to the investigation of the role of DN/GOF alleles in human disease. Here we present aenmd, a software for annotating PTC-containing transcript-variant pairs for predicted escape from NMD. aenmd is user-friendly and self-contained. It offers functionality not currently available …

Taz2 Truncation Confers Overactivation Of P300 And Cellular Vulnerability To Hdac Inhibition, Longxia Xu, Hongwen Xuan, Wei He, Liang Zhang, Mengying Huang, Kuai Li, Hong Wen, Han Xu, Xiaobing Shi

Faculty, Staff and Student Publications

The histone acetyltransferase p300/CBP is composed of several conserved domains, among which, the TAZ2 domain is known as a protein-protein interaction domain that binds to E1A and various transcription factors. Here we show that TAZ2 has a HAT autoinhibitory function. Truncating p300/CBP at TAZ2 leads to hyperactive HAT and elevated histone H3K27 and H3K18 acetylation in cells. Mechanistically, TAZ2 cooperates with other HAT neighboring domains to maintain the HAT active site in a 'closed' state. Truncating TAZ2 or binding of transcription factors to TAZ2 induces a conformational change that 'opens' the active site for substrate acetylation. Importantly, genetic mutations that …

Going Circular: History, Present, And Future Of Circrnas In Cancer, Giuseppina Pisignano, David C Michael, Tanvi H Visal, Radu Pirlog, Michael Ladomery, George A Calin

Faculty, Staff and Student Publications

To date, thousands of highly abundant and conserved single-stranded RNA molecules shaped into ring structures (circRNAs) have been identified. CircRNAs are multifunctional molecules that have been shown to regulate gene expression transcriptionally and post-transcriptionally and exhibit distinct tissue- and development-specific expression patterns associated with a variety of normal and disease conditions, including cancer pathogenesis. Over the past years, due to their intrinsic stability and resistance to ribonucleases, particular attention has been drawn to their use as reliable diagnostic and prognostic biomarkers in cancer diagnosis, treatment, and prevention. However, there are some critical caveats to their utility in the clinic. Their …

Time For Bugs: The Immune Microenvironment And Microbes In Precancer, Mikayla Borthwick Bowen, Beth A Helmink, Jennifer A Wargo, Melinda S Yates

Faculty, Staff and Student Publications

Major advances in our understanding of the tumor immune microenvironment (TIME) in established cancer have been made, including the influence of host-intrinsic (host genomics) and -extrinsic factors (such as diet and the microbiome) on treatment response. Nonetheless, the immune and microbiome milieu across the spectrum of precancerous tissue and early neoplasia is a growing area of interest. There are emerging data describing the contribution of the immune microenvironment and microbiota on benign and premalignant tissues, with opportunities to target these factors in cancer prevention and interception. Throughout this review, we provide rationale for not only the critical need to further …

Prediagnostic Glycoprotein Acetyl Levels And Incident And Recurrent Flare Risk Accounting For Serum Urate Levels: A Population-Based, Prospective Study And Mendelian Randomization Analysis, Amit D Joshi, Natalie Mccormick, Chio Yokose, Bing Yu, Adrienne Tin, Robert Terkeltaub, Tony R Merriman, A Heather Eliassen, Gary C Curhan, Laura M Raffield, Hyon K Choi

Faculty, Staff and Student Publications

OBJECTIVE: To prospectively investigate population-based metabolomics for incident gout and reproduce the findings for recurrent flares, accounting for serum urate.

METHODS: We conducted a prediagnostic metabolome-wide analysis among 105,615 UK Biobank participants with nuclear magnetic resonance metabolomic profiling data (168 total metabolites) from baseline blood samples collected 2006-2010 in those without history of gout. We calculated hazard ratios (HRs) for incident gout, adjusted for gout risk factors, excluding and including serum urate levels, overall and according to fasting duration before sample collection. Potential causal effects were tested with 2-sample Mendelian randomization. Poisson regression was used to calculate rate ratios (RRs) …

Exceptional Responses To Selpercatinib In Ret-Fusion Driven Metastatic Pancreatic Cancer, Deepak Bhamidipati, Sireesha Yedururi, Jason Huse, Sri Veda Chinapuvvula, Jie Wu, Vivek Subbiah

Faculty, Staff and Student Publications

No abstract provided.

Ras Gtpases And Interleaflet Coupling In The Plasma Membrane, Junchen Liu, Neha Arora, Yong Zhou

Faculty, Staff and Student Publications

RAS genes are frequently mutated in cancer. The primary signaling compartment of wild-type and constitutively active oncogenic mutant RAS proteins is the inner leaflet of the plasma membrane (PM). Thus, a better understanding of the unique environment of the PM inner leaflet is important to shed further light on RAS function. Over the past few decades, an integrated approach of superresolution imaging, molecular dynamic simulations, and biophysical assays has yielded new insights into the capacity of RAS proteins to sort lipids with specific headgroups and acyl chains, to assemble signaling nanoclusters on the inner PM. RAS proteins also sense and …

Committing To Genomic Answers For All Kids: Evaluating Inequity In Genomic Research Enrollment., Natalie J. Kane, Ana S A Cohen, Courtney D. Berrios, Bridgette Jones, T Pastinen, Mark A. Hoffman

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Persistent inequities in genomic medicine and research contribute to health disparities. This analysis uses a context-specific and equity-focused strategy to evaluate enrollment patterns for Genomic Answers for Kids (GA4K), a large, metropolitan-wide genomic study on children.

METHODS: Electronic health records for 2247 GA4K study participants were used to evaluate the distribution of individuals by demographics (race, ethnicity, and payor type) and location (residential address). Addresses were geocoded to produce point density and 3-digit zip code maps showing local and regional enrollment patterns. Health system reports and census data were used to compare participant characteristics with reference populations at different …

Worth A Pound Of Cure? Emerging Strategies And Challenges In Cancer Immunoprevention, Saurav D Haldar, Eduardo Vilar, Anirban Maitra, Neeha Zaidi

Faculty, Staff and Student Publications

Cancer immunoprevention applies immunologic approaches such as vaccines to prevent, rather than to treat or cure, cancer. Despite limited success in the treatment of advanced disease, the development of cancer vaccines to intercept premalignant states is a promising area of current research. These efforts are supported by the rationale that vaccination in the premalignant setting is less susceptible to mechanisms of immune evasion compared with established cancer. Prophylactic vaccines have already been developed for a minority of cancers mediated by oncogenic viruses (e.g., hepatitis B and human papillomavirus). Extending the use of preventive vaccines to non-virally driven malignancies remains an …

The Y Of Cancer Sex Differences, Jiexi Li, Ronald A Depinho

Faculty, Staff and Student Publications

No abstract provided.

Cancer Informatics For Cancer Centers: Sharing Ideas On How To Build An Artificial Intelligence-Ready Informatics Ecosystem For Radiation Oncology, Danielle S Bitterman, Michael F Gensheimer, David Jaffray, Daniel A Pryma, Steve B Jiang, Olivier Morin, Jorge Barrios Ginart, Taman Upadhaya, Katherine A Vallis, John M Buatti, Joseph Deasy, H Timothy Hsiao, Caroline Chung, Clifton D Fuller, Emily Greenspan, Kristy Cloyd-Warwick, Samir Courdy, Allen Mao, Jill Barnholtz-Sloan, Umit Topaloglu, Isaac Hands, Ian Maurer, May Terry, Walter J Curran, Quynh-Thu Le, Sorena Nadaf, Warren Kibbe

Faculty, Staff and Student Publications

In August 2022, the Cancer Informatics for Cancer Centers brought together cancer informatics leaders for its biannual symposium, Precision Medicine Applications in Radiation Oncology, co-chaired by Quynh-Thu Le, MD (Stanford University), and Walter J. Curran, MD (GenesisCare). Over the course of 3 days, presenters discussed a range of topics relevant to radiation oncology and the cancer informatics community more broadly, including biomarker development, decision support algorithms, novel imaging tools, theranostics, and artificial intelligence (AI) for the radiotherapy workflow. Since the symposium, there has been an impressive shift in the promise and potential for integration of AI in clinical care, accelerated …

Uncovering The Il-1Β-Pcaf-Nnt Axis: A New Player In Ferroptosis And Tumor Immune Evasion, Qidong Li, Boyi Gan

Faculty, Staff and Student Publications

No abstract provided.

Prognostic Significance Of Trophoblastic Cell Surface Antigen 2 Expression And Pathologic Parameters In Patients With Ampullary Adenocarcinoma, Yujie Zhang, Hua Wang, Michael Overman, Matthew Hg Katz, Huamin Wang

Faculty, Staff and Student Publications

Trophoblastic cell surface antigen 2 (TROP2) has been reported to be up-regulated in several types of carcinomas and is associated with aggressive behavior and poor survival. However, TROP2 expression and its clinical significance in ampullary adenocarcinoma (AA) have not been investigated. We examined TROP2 expression by immunohistochemistry in 112 patients with AAs. The associations of TROP2 expression with clinicopathologic characteristics were evaluated by χ2 analyses or Fisher's exact tests. The associations of TROP2 expression and pathologic parameters with survival were evaluated by the Kaplan-Meier method and univariate and multivariate Cox regression analyses. Eighty-six AAs (76.8%) were positive for TROP2, which …

Phase 2 Trial Of Stereotactic Ablative Radiotherapy For Patients With Primary Renal Cancer, Raquibul Hannan, Mark F Mclaughlin, Laurentiu M Pop, Ivan Pedrosa, Payal Kapur, Aurelie Garant, Chul Ahn, Alana Christie, James Zhu, Tao Wang, Liliana Robles, Deniz Durakoglugil, Solomon Woldu, Vitaly Margulis, Jeffrey Gahan, James Brugarolas, Robert Timmerman, Jeffrey Cadeddu

Faculty, Staff and Student Publications

Background: Most renal cell carcinomas (RCCs) are localized and managed by active surveillance, surgery, or minimally invasive techniques. Stereotactic ablative radiation (SAbR) may provide an innovative non-invasive alternative although prospective data are limited.

Objective: To investigate whether SAbR is effective in the management of primary RCCs.

Design, setting, and participants: Patients with biopsy-confirmed radiographically enlarging primary RCC (≤5 cm) were enrolled. SAbR was delivered in either three (12 Gy) or five (8 Gy) fractions.

Outcome measurements and statistical analysis: The primary endpoint was local control (LC) defined as a reduction in tumor growth rate (compared with a benchmark of 4 …